The proposed research will test the hypothesis that fibronectin mediated phagocytosis is augmented by fibronectin co-factors which are important for optimal reticuloendothelial (RE) phagocytic clearance function. The hypothesis will be addressed by evaluating the nature of a factor present in fibronectin deficient rat plasma that enhances or amplifies fibronectin mediated hepatic macrophage uptake of gelatinized particulate. This fibronectin co-factor will be isolated, purified and biochemically characterized with respect to composition, structure, heat and pH stability and ionic requirements for function in order to clarify the basic mechanisms by which this factor exerts its biological activity. Immunochemical techniques utilizing specific antibody to the co-factor will be established to quantitate blood levels of this factor to further understand the relationship between fibronectin co-factor and support of RES function in vivo as mediated by fibronectin. Although fibronectin has been shown to be important in mediating the phagocytic removal of gelatinized RE test colloids, there are certain pathophysiological processes such as cancer and disseminated intravascular coagulation demonstrating RE clearance deficits, but which are associated with normal or elevated plasma fibronectin levels. In these syndromes, RE depression may be due to depressed co-factor levels. Thus, plasma co-factor levels will be assessed during tumor growth and intravascular coagulation utilizing the immunoassay as well as bioassay. Heparin, which has been demonstrated to be absolutely necessary for the expression of plasma fibronectin opsonic activity in the presence of co-factor as measured by the in vitro liver slice bioassay, will also be systemically studied in the purified plasma fibronectin: co-factor system in vitro. Similar studies will be carried out using an isolated peritoneal macrophage monolayer in addition to the liver slice bioassay to assess the generality of the observed effects. These studies are directed at determining if a plasma fibronectin co-factor and/or heparin deficit existing in the face of normal or elevated plasma fibronectin levels may be etiological in host defense failure observed during disseminated intravascular coagulation and tumor growth.